Using IT to Improve Outcomes for Children Living With Cancer (SyMon-SAYS): Protocol for a Single-Institution Waitlist Randomized Controlled Trial

Background Children and adolescents with cancer may experience multiple disease- and treatment-related symptoms that negatively affect health-related quality of life. Routine symptom surveillance thus constitutes an important component of supportive care in pediatric oncology. The Symptom Monitoring and Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) system will administer, score, interpret, and display the results of symptom assessments captured weekly using patient-reported outcomes presented via the electronic health record (EHR) portal between clinic visits in oncology ambulatory settings, when patients are likely to be more symptomatic. This study is testing a digital system for routine symptom surveillance that includes EHR-based reports to clinicians and alerts for severe symptoms. Objective In this randomized trial, we are examining the effects of the SyMon-SAYS system on perceived barriers to symptom management, self-efficacy, and symptom severity. Better self-management and timely clinical intervention to address symptoms promote adherence to treatment plans, strengthen child and parent self-efficacy, improve interactions between children, parents, and their clinical providers, and optimize clinical outcomes. Methods The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptoms to clinicians using EHR (Epic) messaging functionalities. Children (aged 8 to 17 years) complete the weekly symptom assessment and review the symptom report by logging into the patient portal (Epic MyChart). This single-institution waitlist randomized controlled trial is recruiting 200 children (aged 8-17 years) with cancer and their parents, guardians, or caregivers. Participating dyads are randomly assigned to receive the intervention over 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then an 8-week SyMon-SAYS intervention). Analyses will (1) evaluate the efficacy of SyMon-SAYS at week 8 and the maintenance of those effects at week 16; (2) evaluate factors associated with those efficacy outcomes, including contextual factors, adherence to the SyMon-SAYS intervention, demographic characteristics, and clinical factors; and (3) evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care. Results Data collection is currently in progress. We hypothesize that at 8 weeks, those receiving the SyMon-SAYS intervention will report decreased parent-perceived barriers to managing their children’s symptoms, increased parent and child self-efficacy, decreased child symptom burden, and ultimately better child health-related quality of life, compared to waitlist controls. Feasibility, acceptability, and engagement from the perspectives of the children with cancer, their parents, and their clinicians will be examined using mixed methods. Conclusions We anticipate that this system will facilitate prompt identification of problematic symptoms. Additionally, we hypothesize that with the availability of graphical symptom reports over time, and timely provider responses, children or parents will become better informed and take an active role in managing their symptoms, which will further improve clinical outcomes. Trial Registration ClinicalTrials.gov NCT04789720; https://clinicaltrials.gov/study/NCT04789720 International Registered Report Identifier (IRRID) DERR1-10.2196/50993

CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form The CONSORT-EHEALTH checklist is intended for authors of randomized trials evaluating web-based and Internet-based applications/interventions, including mobile interventions, electronic games (incl multiplayer games), social media, certain telehealth applications, and other interactive and/or networked electronic applications. Some of the items (e.g. all subitems under item 5 -description of the intervention) may also be applicable for other study designs.
The goal of the CONSORT EHEALTH checklist and guideline is to be a) a guide for reporting for authors of RCTs, b) to form a basis for appraisal of an ehealth trial (in terms of validity) CONSORT-EHEALTH items/subitems are MANDATORY reporting items for studies published in the Journal of Medical Internet Research and other journals / scienti c societies endorsing the checklist.
As the CONSORT-EHEALTH checklist is still considered in a formative stage, we would ask that you also RATE ON A SCALE OF 1-5 how important/useful you feel each item is FOR THE PURPOSE OF THE CHECKLIST and reporting guideline (optional).
Mandatory reporting items are marked with a red *. In the textboxes, either copy & paste the relevant sections from your manuscript into this form -please include any quotes from your manuscript in QUOTATION MARKS, or answer directly by providing additional information not in the manuscript, or elaborating on why the item was not relevant for this study. yes: all primary outcomes were signi cantly better in intervention group vs control partly: SOME primary outcomes were signi cantly better in intervention group vs control no statistically signi cant difference between control and intervention potentially harmful: control was signi cantly better than intervention in one or more outcomes inconclusive: more research is needed Other: Approx. Percentage of Users (starters) still using the app as recommended after Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if o ine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.
C l e a r s e l e c t i o n Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Study Protocol for the Using Information Technology to Improve Outcomes for Children Living with Cancer (SyMon-SAYS)" https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 10/84 subitem not at all important 1 2 3 4 5 essential 1a-ii) Non-web-based components or important co-interventions in title Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support").
C l e a r s e l e c t i o n Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Using Information Technology to Improve Outcomes for Children Living with Cancer (SyMon-SAYS)" This is an information technology system which is integrated into the electronic health record through which participants provide data using EPIC MyChart, which can be used from any device with internet connectivity. Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptons to clinicians using EHR (Epic) messaging functionalities.Children (ages 8 to 17) complete the weekly symptom assessment and review of the symptom report by logging into the patient portal (Epic MyChart). " Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptons to clinicians using EHR (Epic) messaging functionalities.Children (ages 8 to 17) complete the weekly symptom assessment and review of the symptom report by logging into the patient portal (Epic MyChart Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study No, because data collection is ongoing and the purpose of the paper is to describe the protocol, not the final results of the intervention.  Does your paper address subitem 1b-v?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study No, because data collection is ongoing and the purpose of the paper is to describe the protocol, not the final results of the intervention. METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "In this single institution modified waitlist control randomized trial, 200 children (ages 8-17) with cancer and their parents will participate for 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then 8-week SyMon-SAYS intervention). Our study is addressing the following specific aims: • Aim 1: Evaluate efficacy of SyMon-SAYS after 8 weeks and its maintenance effects at week-16. We hypothesize that Group A (versus Group B) will report decreased parentperceived barriers to managing their children's symptoms, decreased child symptom burden, increased child and parent self-efficacy, and ultimately increased child HRQoL at week-8. We expect that these differences between Groups A and B will be narrowed at week-16 when Group B completes the 8-week SyMon-SAYS intervention. • Aim 2: Evaluate factors associated with Aim 1 efficacy outcomes, including but not limited to 1) contextual factors; 2) adherence to the SyMon-SAYS intervention, and 3) symptom communication between clinicians and children/families. • Aim 3: Evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care. We will identify predictors of adherence and model their association by using ordinal regressions. Preference of SyMon-SAYS versus usual care will be evaluated using responses from SyMon-SAYS program evaluation. This understanding will help to develop individualized symptom management approaches for better quality and outcomes of care in pediatric oncology ambulatory settings." https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 23/84 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The study design is shown in Figure 2. To increase utility and compliance of clinicians, children and parents, the SyMon-SAYS system was built within the Ann and Robert H. Lurie Children's Hospital of Chicago (Lurie) EHR (Epic). Participants (parents and children) complete assessments in-clinic using an iPad with internet access at baseline, week-8 and week-16. They are randomly assigned to Group A (weeks 1-16: SyMon-SAYS intervention) or Group B (weeks 1-8: usual care; weeks 9-16: SyMon-SAYS intervention) after the baseline assessment. During the intervention weeks (either weeks 1-16 or weeks 9-16), participants complete a weekly symptom assessment wherever they have internet access using their MyChart patient portal, accessible via smartphone, tablet or computer. " Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study After study commencement, the eligibility criteria for parents was expanded to include Spanish-speaking parents to expand the scope of eligible patient/parent dyads.
"A parent of eligible children (father, mother or legal guardians) is eligible for the study if s/he demonstrates sufficient fluency in English or Spanish to understand and provide informed consent (either in clinic or via remote recruitment), agrees to complete assessments at all time-points, and has sufficient cognitive and motor abilities to complete surveys via an electronic device (e.g., smartphone, iPAD, etc) or computer. Only one parent per child participates in the study." Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study •" Patients. Eligible participants are those with a diagnosis of a malignancy (including children with primary brain tumors), who are currently receiving cancer-directed therapy or are within 6 months of completing cancer-directed therapy, and who are between 8 and 17 years old at the time of enrollment, English-speaking, have sufficient cognitive and motor abilities to complete surveys via an electronic device (e.g., smartphone, iPAD, etc) or computer, and able and willing to sign assent forms (for those between 12-17 years of age).
No formal cognitive testing is conducted; eligibility based on cognitive status is determined by the judgment of their clinicians. Utilization of any assistive device to complete the assessment is acceptable and will be documented. • Parents. A parent of eligible children (father, mother or legal guardians) is eligible for the study if s/he demonstrates sufficient fluency in English or Spanish to understand and provide informed consent (either in clinic or via remote recruitment), agrees to complete assessments at all time-points, and has sufficient cognitive and motor abilities to complete surveys via an electronic device (e.g., smartphone, iPAD, etc) or computer. Only one parent per child participates in the study. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Patients "have sufficient cognitive and motor abilities to complete surveys via an electronic device (e.g., smartphone, iPAD, etc) or computer," Parents "has sufficient cognitive and motor abilities to complete surveys via an electronic device (e.g., smartphone, iPAD, etc) or computer. " "After enrollment, study personnel demonstrate how to complete baseline assessments using an iPad. IP participants are trained on accessing SyMon-SAYS using the Epic MyChart patient portal. " subitem not at all important 1 2 3 4 5 essential 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. o ine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email con rmation, phone calls) were used to detect/prevent these. Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Patient participants were recruited in-person in-clinic by study personnel following determination of eligiblity in conjuction with treating clinicians. "We are recruiting 200 children with cancer from hematology, oncology and brain tumor clinics at Ann & Robert Lurie Children's Hospital, Chicago " Clinicians were enrolled as participants in the study in person in-clinic by study personnel. "Oncology clinical providers who treat participants are also enrolled in the study and provide informed consent as research participants per IRB's requirements at Lurie Children's Hospital." "After enrollment, study personnel demonstrate how to complete baseline assessments using an iPad. IP participants are trained on accessing SyMon-SAYS using the Epic MyChart patient portal." "Parents of IP participants are informed that the study team will send a reminder to them one day prior to the chosen day regarding the upcoming assessment. " Although symptom assessments are completed via Epic MyChart, study personnel communicate with participants to provide reminders to complete assessments and provide participants with their longitudinal symptom reports in-clinic. Does your paper address subitem 4a-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 31/84 "Study personnel explain the aims of the study, what is involved in study participation, and the potential risks and benefits of the study to the potential participants (children, their parents, and providers) so that they can make an informed decision as to whether they wish to participate. This explanation is done in plain, non-exculpatory language that is easy for parents, patients, and providers to understand. Additionally, all participants who are approached for participation in this study are informed that participation in this study is voluntary, and that a decision to not participate will not jeopardize or affect their medical care or their employment status (for clinical providers) in any way. They are informed that they are also free to discontinue participation at any time during the study with no adverse impact to their treatment, overall care or employment status. Clinical provider participants are also be informed that their decision to participate or discontinue participation will not impact their employment status, and the data they provide during the course of their participation will be used for the purpose of this research study only and will not be made available to the institution or any managing or supervisory personnel (e.g., for their merit reviews).

Risks and/or Ethical Issues
There are no known social or legal risks to subjects who participate in this study. Our experience with data collection using similar questions has indicated that few (less than 1% of over 15,000 participants over more than 20 years) are distressed by the content of the questions posed to them. Participants are advised that if they become upset by the questions, they will have the option to talk with a trained mental health professional. The PI will be notified of all requests for consultation with a mental health professional.
There is a slight possibility that enhanced monitoring of symptoms could lead to an increase in anxiety. Yet our feasibility study showed that SyMon-SAYS significantly decreased children's anxiety level at week-4 (p=0.046; unpublished data). Furthermore, in the current study, children's emotional distress (worry and sadness) are included in the weekly assessments and are monitored closely. As with all symptoms being monitored, an alert is generated when children's reports of worry and/or sadness meet or exceed the pre-established threshold. Clinicians are notified within 24 hours and take appropriate actions to respond to these symptom experiences. In addition, in consultation with the site clinical team, the study team reserves the right to withdraw any participant for whom there is concern that the intervention is having an adverse effect.
Measures to Protect Privacy and Confidentiality of Participants Study personnel enroll patients and their parents and assign each patient and parent participant their unique identification (ID) code, which is used for identifying and tracking participants throughout the study. Parent codes are linked to corresponding patient (child/adolescent) codes. Clinician participants are recruited by Drs. Lai and Lenzen and are also be assigned a unique ID code. All data collected from all participants is linked with this unique identifier and not the participants. Information of linking IDs to participants is saved as a separate password protected file that only the PI and the study coordinator can access." Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Participants (parents and children) complete assessments in-clinic using an iPad with internet access at baseline, week-8 and week-16. They are randomly assigned to Group A (weeks 1-16: SyMon-SAYS intervention) or Group B (weeks 1-8: usual care; weeks 9-16: SyMon-SAYS intervention) after the baseline assessment. During the intervention weeks (either weeks 1-16 or weeks 9-16), participants complete a weekly symptom assessment wherever they have internet access using their MyChart patient portal, accessible via smartphone, tablet or computer. " Does your paper address subitem 5-i?

4b-ii) Report how institutional affiliations are displayed
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

5-ii) Describe the history/development process
Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results.
Does your paper address subitem 5-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial. Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).

Does your paper address subitem 5-iii?
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5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study subitem not at all important 1 2 3 4 5 essential 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screencapture video, and/or providing owcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scienti c reporting.
Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.

Does your paper address subitem 5-vi?
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5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speci c group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).
C l e a r s e l e c t i o n Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "To increase utility and compliance of clinicians, children and parents, the SyMon-SAYS system was built within the Ann and Robert H. Lurie Children's Hospital of Chicago (Lurie) EHR (Epic). Participants (parents and children) complete assessments in-clinic using an iPad with internet access at baseline, week-8 and week-16. They are randomly assigned to Group A (weeks 1-16: SyMon-SAYS intervention) or Group B (weeks 1-8: usual care; weeks 9-16: SyMon-SAYS intervention) after the baseline assessment. During the intervention weeks (either weeks 1-16 or weeks 9-16), participants complete a weekly symptom assessment wherever they have internet access using their MyChart patient portal, accessible via smartphone, tablet or computer. " Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "After enrollment, study personnel demonstrate how to complete baseline assessments using an iPad. IP participants are trained on accessing SyMon-SAYS using the Epic MyChart patient portal. IP participants are provided with a card containing their unique ID code and brief instructions for using the system. The card also contains the study personnel's name and telephone number for any questions that might arise. IP participants are asked to choose a standard day of the week to access the system and complete their weekly symptom assessment. Parents of IP participants are informed that the study team will send a reminder to them one day prior to the chosen day regarding the upcoming assessment. IP participants are given a window of one business day before and two business days after their preferred day to access the system. IP participants complete the SyMon-SAYS symptom checklist (symptom items are available in Appendix) every week for 8 weeks through Epic MyChart via mobile app, computer or tablet. If IP participants do not access the system by midnight of the preferred day, study personnel contact the parent the following day (preferred day +1 business day) and remind them to complete the assessment or prompt their child to do so. If the participant does not access the system by midnight of the day following their preferred day, study personnel again attempt to contact the parent by phone (preferred day +2 business days) to remind them or prompt their child to access the system. Study personnel ascertain any issues that might be related to noncompliance (e.g., hospitalization) during reminder calls. " "When a child's symptom score exceeds the pre-set severity threshold (i.e., scores 3 or higher), the system will generate an email alert through Epic messaging to the study team with the child's study ID. Upon receipt of an alert, the study coordinator will access the report in Epic and notify the child's treating team to determine whether a call is needed. If needed, the nurse will contact the parent within one business day to ascertain their child's current status (see Figure 3 for study schema). The nurse will document actions taken in Epic." "After children and parents complete the week 8 and week 16 assessments, study personnel print out symptom reports (Group A: week 8 and week 16; Group B: week 16 only) in clinic and deliver them to parents of IP participants and treating provider prior to their appointment (either week-8 or week-16). Parents are also be encouraged to review the online version of the report by logging into MyChart prior to clinical visits. Clinicians in the child's care team are able to review this report in children's medical record, where it is stored along with other usual clinical data. These reports reflect children's cumulative symptom scores between baseline, week-8 and week-16 (Group A in Figure  2) or between week-8 to week-16 (Group B). Parents are encouraged to discuss the

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.

Does your paper address subitem 5-ix?
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5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).

Does your paper address subitem 5-x?
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5-xi) Report any prompts/reminders used
Report any prompts/reminders used: Clarify if there were prompts (letters, emails, phone calls, SMS) to use the application, what triggered them, frequency etc. It may be necessary to distinguish between the level of prompts/reminders required for the trial, and the level of prompts/reminders for a routine application outside of a RCT setting (discuss under item 21 -generalizability).
C l e a r s e l e c t i o n Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "IP participants are asked to choose a standard day of the week to access the system and complete their weekly symptom assessment. Parents of IP participants are informed that the study team will send a reminder to them one day prior to the chosen day regarding the upcoming assessment. IP participants are given a window of one business day before and two business days after their preferred day to access the system. IP participants complete the SyMon-SAYS symptom checklist (symptom items are available in Appendix) every week for 8 weeks through Epic MyChart via mobile app, computer or tablet. If IP participants do not access the system by midnight of the preferred day, study personnel contact the parent the following day (preferred day +1 business day) and remind them to complete the assessment or prompt their child to do so. If the participant does not access the system by midnight of the day following their preferred day, study personnel again attempt to contact the parent by phone (preferred day +2 business days) to remind them or prompt their child to access the system. " Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "After enrollment, study personnel demonstrate how to complete baseline assessments using an iPad. IP participants are trained on accessing SyMon-SAYS using the Epic MyChart patient portal. IP participants are provided with a card containing their unique ID code and brief instructions for using the system. The card also contains the study personnel's name and telephone number for any questions that might arise.
Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "For the quantitative methodology, we will calculate percentage of weekly symptom assessments that children complete, the number of weekly symptom scores that exceed a prior threshold to trigger alerts, as well as clinician documentation to symptom alerts in the EHR. In addition, a subset of participants (parent/child dyads) will be interviewed to obtain their feedback on the symptom report discussions with their clinician and their experience participating in the SyMon-SAYS study at the end of the intervention phase. Children and parents will be interviewed independently. Efforts will be made to balance gender (children and parents), ages (children), clinical variables of children as well as English-and Spanishspeaking participants (all children are English-speaking). Participants whose parents speak Spanish will be interviewed in Spanish.
At the completion of the study, clinicians, including attending physicians, fellows, advanced practice nurses/physician assistants, and registered nurses, will also be interviewed by either individual interviews (via telephone) or email survey to obtain their feedback on the symptom report, the study, and suggestions on how to make it more accessible/child friendly.
We plan to interview up to 30 parent/child dyads and up to 20 clinicians. The telephone interviews will be recorded for transcription and subsequent summary of feedback. Members of the study team will use selective qualitative analysis methods and an iterative coding process to identify common themes and develop coding rules to apply to interviewees' comments. The comments will then be compiled and summarized in frequency tables denoting the number of times certain responses emerge. Both frequency and the relative importance placed on the theme will be used evaluate usability, acceptability, and engagement along with quantitative results.

Adherence to Intervention
The adherence to the SyMon-SAYS Intervention will be evaluated by using the percentage of dyads completing the assessments at all time-points, excluding those who are off-study or deceased.

Measures used for Primary and Secondary Outcomes Modified Symptom Management Barriers Questionnaire (SMBQ)
The modified SMBQ is a 23-item tool designed to assess the attitude (perceived barriers) of parents with children diagnosed with cancer towards the assessment and management of their child's symptoms. The SMBQ comprises items that encompass various recognized barriers to achieve effective symptom management. The original version of the SMBQ[9] items were devised with input from experts in symptom assessment and management and interviews with patients and their spouses. The study team made adjustments to the items to ensure their suitability for parents of children with cancer, such as replacing the pronoun "I" with "my child".
Pediatric PROMIS (pedsPROMIS) Change in HRQOL over time will be analyzed by examining changes in the pediatric PROMIS measures. We will administer CATs of the domains in the PROMIS Pediatric Profile:[50] 1) physical function-mobility, 2) physical function-upper extremity, 3) depressive symptoms, 4) anxiety, 5) anger, and 6) relationship with peers. The pedsPROMIS offer good reliability across 2-3 standard deviations of the experiences of children 8-17 years old. subitem not at all important 1 2 3 4 5 essential 6b) Any changes to trial outcomes after the trial commenced, with reasons 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Describe whether, how, and when qualitative feedback from participants was obtained (e.g., through emails, feedback forms, interviews, focus groups).

Does your paper address subitem 6a-iii?
Copy and paste relevant sections from manuscript text

Your answer
Does your paper address CONSORT subitem 6b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study There have been no changes to trial outcomes. Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "We will use a stratified block randomization approach. Participants are randomly assigned to Group A or B, stratified by gender, age, and cancer types. To achieve allocation concealment, the computer-based data management system (REDCap) assigns participants to one of two groups after the study enrollment procedures.
Participants are informed of their group assignment (Group A or B) after the baseline https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 54/84 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "We will use a stratified block randomization approach. Participants are randomly assigned to Group A or B, stratified by gender, age, and cancer types. To achieve allocation concealment, the computer-based data management system (REDCap) assigns participants to one of two groups after the study enrollment procedures.
Participants are informed of their group assignment (Group A or B) after the baseline Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "We will use a stratified block randomization approach. Participants are randomly assigned to Group A or B, stratified by gender, age, and cancer types. To achieve allocation concealment, the computer-based data management system (REDCap) assigns participants to one of two groups after the study enrollment procedures.
Participants are informed of their group assignment (Group A or B) after the baseline https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 55/84 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Participants are enrolled by members of the study team.
"To achieve allocation concealment, the computer-based data management system (REDCap) assigns participants to one of two groups after the study enrollment procedures.
Participants are informed of their group assignment (Group A or B) after the baseline assessment." 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering cointerventions (if any). Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Neither participants, clinical providers, nor members of the study team were blinded.
11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectations -discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".
Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 57/84 11b) If relevant, description of the similarity of interventions (this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "Participants (parents and children) complete assessments in-clinic using an iPad with internet access at baseline, week-8 and week-16. They are randomly assigned to Group A (weeks 1-16: SyMon-SAYS intervention) or Group B (weeks 1-8: usual care; weeks 9-16: SyMon-SAYS intervention) after the baseline assessment. During the intervention weeks (either weeks 1-16 or weeks 9-16), participants complete a weekly symptom assessment " https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_OimqcS64RdfIAFvmrTSkZQL2-3O8O9hrL5Sw/viewform?pli=1 58/84 Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Evaluate efficacy of SyMon-SAYS after 8 weeks and its maintenance effects at week-16: We will fit mixed effects models for repeated measures. We will control for multiplicity among co-primary outcomes with the Benjamini-Hochberg procedure.
[53] Regarding from baseline to week 8 (Group A) or from week 9 to week 16 (Group B) estimated by calculating the area under the curve (AUC) of each symptom score plotted over time for each participant. The AUC will be then divided by the total time to rescale back to the original units. We will calculate a p-value for differences in AUC curves between arms with a Wilcoxon rank test.
Evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care: We will identify predictors of intervention adherence and preference using ordinal regression models using data from both groups' intervention phases (weeks 1-8 for group A, weeks 9-16 for group B). Based on number of weekly system assessments completed, patients will be classified as high adherence (completed 7 or 8 weekly assessments), intermediate adherence (completed 3-6 weekly assessments), or low adherence (completed 1 or 2 or fewer weekly assessments). Additionally, we will repeat the same analysis using data from week 9-week 16 from Group A to explore whether the group membership (i.e., high, intermediate or low adherence) changed between phase 1 (baseline to week 8) and phase 2 (week 9-week 16) as well as predictors associated with the group membership. subitem not at all important 1 2 3 4 5 essential 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses 12a-i) Imputation techniques to deal with attrition / missing values Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).
C l e a r s e l e c t i o n Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "If necessary, multiple imputation of weekly symptom data for secondary endpoints by chained equations (MICE) will be used to impute missing data." Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study We will explore the associations of demographic variables (e.g., gender), individual factors (e.g., health literacy) and clinical characteristics (e.g., intensity of treatment) on primary outcomes.
We will code individual patients as having improved or not improved by a clinically important threshold and examine whether patient and parent contextual factors are associated with improvement on each outcome (each modeled separately) using multivariable logistic regression models. "We will identify predictors of intervention adherence and preference using ordinal regression models using data from both groups' intervention phases (weeks 1-8 for group A, weeks 9-16 for group B). Based on number of weekly system assessments completed, patients will be classified as high adherence (completed 7 or 8 weekly assessments), intermediate adherence (completed 3-6 weekly assessments), or low adherence (completed 1 or 2 or fewer weekly assessments). "

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline) Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study This is not applicable because enrollment and data collection are ongoing.
Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study This is not applicable because enrollment and data collection are ongoing. subitem not at all important 1 2 3 4 5 essential 16-i) Report multiple "denominators" and provide definitions Report multiple "denominators" and provide de nitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speci c pre-de ned time points of interest (in absolute and relative numbers per group). Always clearly de ne "use" of the intervention.
Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Not applicable. Enrollment and data collection are ongoing. 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval)

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).

Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study 17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational de nitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is de ned (e.g., timeout after idle time) [1] (report under item 6a).

18-i) Subgroup analysis of comparing only users
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).

Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Does your paper address subitem 19-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study subitem not at all important 1 2 3 4 5 essential 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use).
Does your paper address subitem 22-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Study questions are summarized but results are not reported because enrollment and data collection are ongoing.

Does your paper address subitem 22-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Your answer

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events.
Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study "The study has some potential caveats that will need to be considered in interpreting the findings and should be addressed in future research. "

21-i) Generalizability to other populations
Generalizability to other populations: In particular, discuss generalizability to a general Internet population, outside of a RCT setting, and general patient population, including applicability of the study results for other organizations Does your paper address subitem 21-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other cointerventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study About the CONSORT EHEALTH checklist X27-i) State the relation of the study team towards the system being evaluated In addition to the usual declaration of interests ( nancial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention.
C l e a r s e l e c t i o n Does your paper address subitem X27-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or brie y explain why the item is not applicable/relevant for your study The authors having nothing to disclose. As a result of using this checklist, did you make changes in your manuscript? * What were the most important changes you made as a result of using this checklist?

Your answer
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